Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Renal Insufficiency

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Cisplatin

Tubulin Modulators

Vinblastine

Antimetabolites

Antimitotic Agents

* Vinflunine 280 or 250 mg/m2, IV administration over 20 minutes (starting dose based on baseline creatinine clearance value), Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal
* Gemcitabine 750 or 1000 mg/m2, IV administration over 30 minutes (starting dose based on baseline creatinine clearance value), Day 1 and 8 every 3 weeks up to progression or unacceptable toxicity or patient's refusal

Vinflunine, Gemcitabine

* Vinflunine 280 or 250 mg/m2, IV administration over 20 minutes (starting dose based on baseline creatinine clearance value), Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal
* Carboplatin AUC 4.5, IV administration over 60 minutes, Day 1 every 3 weeks up to progression or unacceptable toxicity or patient's refusal

Vinflunine, Carboplatin

Maria De Santis, MD

Stéphane Culine, MD

This study is assessing the combination of well known cytotoxics with a novel anti-cancer agent that could be administered as monotherapy without renal toxicity in patients with renal impairment presenting with advanced or metastatic urothelial carcinoma previously treated with a platinum-based regimen. The intent of this study is to clarify the benefit/risk ratio of the two most promising associations of cytotoxics including the novel therapeutic agent, vinflunine: vinflunine-gemcitabine and vinflunine-carboplatin.

Gemcitabine and carboplatin have been the most studied and used anticancer agents in cisplatin-unfit patients with advanced urothelial carcinoma. Both agents previously demonstrated clinical activity as single agent and/or as part of combination regimen in patients with advanced or metastatic disease even if clinical benefits and survival remains limited in this setting for this population.

The purpose of this study is to test in a randomized trial enrolling patients with renal impairment or moderate congestive heart failure two combinations of a novel cytotoxic agent, vinflunine, one with gemcitabine and another with carboplatin in order to determine the most promising combination in the first line treatment of advanced/metastatic urothelial carcinoma.

JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin

Randomized Phase II Study Assessing the Combination of Vinflunine With Gemcitabine and Vinflunine With Carboplatin in Patients Ineligible to Cisplatin With Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

Assessment of lesions (measurable and non-measurable) should be performed at baseline and every 6 weeks (assessment interval).

Evaluable patients: all baseline lesions must have been assessed at least once after the second cycle (6 weeks); patients who progress before the first evaluation will be considered as early progression.

Primary analysis is planned on the intent to treat population, secondary analysis being performed on the evaluable population.

Assessment of lesions (measurable and non-measurable) should be performed at baseline and every 6 weeks (assessment interval).

Evaluable patients: all baseline lesions must have been assessed at least once after the second cycle (6 weeks); patients who progress before the first evaluation will be considered as early progression.

Tumor assessment at baseline and then every 6 weeks, until tumor progression. Duration of disease control according to investigator will be calculated among the responders and stable patients from the date of randomisation until the documentation of progression or death due to any cause. Patients who are lost to follow-up without progression, or reach the time point of analysis without a known record of progression or death will have the duration of disease control censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

Tumor assessment at baseline and then every 6 weeks, until tumor progression. Duration of response will be calculated among the responders (i.e. CR and PR) . Patients who are lost to follow-up, or reach the time point of analysis without a known record of progression or death will have the duration of response censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

Tumor assessment at baseline and then every 6 weeks. Will be calculated among the responders (i.e. CR and PR)

Tumor assessment (RECIST) every 6 weeks. Patients who reach the time point of analysis without failure as defined above will have the time to treatment failure censored at the date of last tumour assessment or last contact of a follow-up not showing progression. Patients who discontinued treatment for other reason and who are lost to follow-up will be censored at the date of last contact.

Tumor assessment every 6 weeks (RECIST).Patients who are lost to follow-up, or reach the time point of analysis without a known record of progression or death will have the progression-free survival censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occur last.

Data recording every 3 months. For patients who have not died, survival time will be censored at the date of last news (i.e: date of last administration, tumor assessment, clinical examination, haematological or biochemistrical assessment or date of last contact).

Population: all treated patients unless the patient is lost to follow-up immediately after the start of the treatment. The patients will be analysed in the treatment arm they actually received.

The NCI-CTC classification version 2.0 will be used to classify toxicities. Maximum grade or severity will be reported by cycle and by patient for each MedDRA Preferred Term. Analyses will be performed both regardless the relationship to treatment and related to treatment.

Biochemical toxicities: the worst CTCAE version 2.0 grade will be analysed according to the grade present at baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin	NCT01599013	Bladder Transit...	Vinflunine, Gem... Vinflunine, Car...	18 Years - 79 Years	Pierre Fabre Medicament
JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin	NCT01599013	Bladder Transit...	Vinflunine, Gem... Vinflunine, Car...	18 Years - 79 Years	Pierre Fabre Medicament

Spots Global Cancer Trial Database for vinflunine, gemcitabine